Established in 1999, the UIC/NIH Center for Botanical Dietary Supplements Research (UIC Botanical Center) investigates the safety and mechanisms of action of botanical dietary supplements consumed by American women for the purpose of maintaining good health and quality of life, especially during the transition to and through menopause. The UIC Botanical Center involves a synergistic team of multi-disciplinary investigators with complementary expertise who are organized into three Projects, an Administrative Core and three research Cores as follows: Project 1: Metabolomic Analysis, Design and Standardization of Botanical Extracts; Project 2: Botanicals Affect Resilience Through Modulation of Estrogen Carcinogenic Pathways; Project 3: Botanical Dietary Supplements - Metabolism and Safety in Women; Core A: Administration; Core B: Botanical Integrity; Core C: Bioassay; and Core D: Analytical. Our portfolio of botanicals for study was selected based on prevalence of use by American women and the documented ability of these botanicals to enhance resilience. These botanicals will include milk thistle (Silybum marianum), Valerian (Valeriana officinalis), Dang Gui (Angelica sinensis), Maca (Lepidium meyenii), licorice (Glycyrrhiza species), Chaste Tree Berry (Vitex agnus-castus), hops (Humulus lupulus), Kwao Keur (Pueraria mirifica), wild yam (Dioscorea villosa), rose root (Rhodiola rosea), and Five Flavor Berry (Schisandra chinensis). We propose to develop metabolomics tools for the advanced chemical and biological standardization of botanical dietary supplements in Project 1, study estrogenic and chemoprevention (resilience) mechanisms of action in Project 2, and investigate metabolism and potential for drug-botanical interactions (safety) both in vitro and in women in Project 3. Within each Project, there are highly innovative approaches that will be utilized including the knock- out/knock-in (DESIGNER) extract technology of Project 1; the concept in Project 2 that anti-inflammatory botanical dietary supplements can lower cytokine levels and thereby prevent formation of genotoxic estrogen metabolites; and the safety studies in Project 3 that involve high-throughput UHPLC-MS/MS detection of electrophilic metabolites and high-throughput cocktail assays of cytochrome P450 inhibition. With strong institutional support (personnel, space, services, and equipment), a commitment to educating the next generation of experts in botanical dietary supplements, an interactive team of researchers located within a single institution, and a synergist approach, we expect to sustain our high level of productivity as reflected in over 200 publications and 40 PhD and MS graduates. These studies will greatly impact the design of optimized botanical supplements and drive the long-term goal of the UIC Botanical Center toward developing safe and effective botanical dietary supplements for women's health.